Calcium homeostasis in mouse fibroblast cells: affected by U‐73122, a putative phospholipase Cβ blocker, via multiple mechanisms

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Abstract
1 The inhibitory effects of the putative phospholipase Cβ inhibitor, U-73122, on ligand-induced and thapsigargin-induced [Ca2+]i transients were investigated in mouse fibroblast cells (the L line). 2 Ca2+ release from intracellular stores was stimulated either by ATP (and also by UTP or ADP) working through the activation of a P2U receptor, or by lysophosphatidic acid, which elicited a more pronounced response. 3 U-73122 inhibited the Ca2+ mobilization produced by all the agonists in a dose-dependent manner, consistent with a mode of action involving phospholipase C inhibition. 4 In addition, however, U-73122 slowed the kinetics of intracellular Ca2+ release induced by the Ca2+-ATPase inhibitor, thapsigargin, and reduced the influx of Ca2+ across the plasma membrane, following stimulation of store-dependent influx by the latter. 5 We conclude that U-73122 has multiple sites of action, all of which can lead to a change in Ca2+ homeostasis. Thus, particular caution is recommended when employing this agent and when interpreting the results obtained.